Procalcitonin (PCT) Predicts Worse Outcome in Patients with Chronic Heart Failure with Reduced Ejection Fraction (HFrEF).

INTRODUCTION: Procalcitonin (PCT) is an excellent marker of sepsis but was not extensively studied in cardiology. The present study investigated PCT plasma concentration in patients with chronic heart failure with reduced ejection fraction (HFrEF) and its prognostic value during 24-month follow-up. MATERIAL AND METHODS: Study group consisted of 130 patients with HFrEF (LVEF ≤ 45%) and 32 controls. PCT level was assessed on admission in all patients. Telephone follow-up was performed every three months over a period of 2 years. Endpoints were death of all causes and readmission for HFrEF exacerbation. RESULTS: HFrEF patients had significantly higher PCT concentration than controls (166.95 versus 22.15 pg/ml; p < 0.001). Individuals with peripheral oedema had increased PCT comparing to those without oedema (217.07 versus 152.12 pg/ml; p < 0.02). In ROC analysis, PCT turned out to be a valuable diagnostic marker of HFrEF (AUC 0.91; p < 0.001). Kaplan-Meier survival curves revealed that patients with PCT in the 4th quartile had significantly lower probability of survival than those with PCT in the 1st and 2nd quartiles. In univariate, but not multivariate, analysis, procalcitonin turned out to be a significant predictor of death during 24-month follow-up. (HR 1.002; 95% CI 1.000-1.003; p < 0.03). CONCLUSIONS: Elevated PCT concentration may serve as another predictor of worse outcome in patients with HFrEF.

Immunomodulatory effects of Lactobacillous plantarum and Helicobacter pylori CagA⁺ on the expression of selected superficial molecules on monocyte and lymphocyte and the synthesis of cytokines in whole blood culture.

Helicobacter pylori (H. pylori) infections are usually superficial and clinically asymptomatic, but in approximately 10-20% cases it can be more aggressive and associated with other pathologies. The reason for weak or strong pro-inflammatory responses in gastric mucosa that occur during H. pylori infection is not understood. Combined treatment, including antibiotic therapy with administration of probiotic bacteria along, considerably improves the effectiveness of H. pylori eradication and reduces the relapse rate. Thus, the aim of this study was to analyze the effect of Lactobacillus plantarum (L. plantarum) and/or H. pylori CagA(+) on leucocytes in whole blood cultures. This study revealed how selected strains of H. pylori and L. plantarum modulate expression of chosen membrane markers of monocytes and lymphocytes, and the cytokine synthesis of in vitro cultures. The level of IFN-γ was higher in cultures stimulated with L. plantarum than in combination of this two examinated strains. We also observe the tendency to increase the level of IFN-γ by L. planatrum in relation to cells stimulated by H. pylori. In contrast, both H. pylori alone and in combination with L. plantarum had a strong modulatory effect on the synthesis of interleukin-10. Moreover lymphocytes with higher expression of CD25 and CD58 receptors was observed only in those cultures that were stimulated with L. plantarum strain alone or in combination with H. pylori. Effects exerted on the immune system, both in terms of natural and adaptive response, constitute the only functional criterion of probiotic bacteria. The immunostimulant effects documented in this study suggest that Lactobacillus spp. can restore immune function of mucosal membrane during symptomatic infection with H. pylori.

Combined effect of different lactic acid bacteria strains on the mode of cytokines pattern expression in human peripheral blood mononuclear cells.

The balance between immunogenic and tolerogenic activities in human immune system strongly depends on microflora-induced pro-and anti-inflammatory activities. Lactic acid bacteria (LAB) are important components of microflora. The interactions of the different strains of LAB and the cells of immune system are largely unknown. To assess if LAB strains composition would have an effect on the cellular responses profile (proliferation, cytokines synthesis) peripheral blood mononuclear cells (PBMC) model system was used. PBMC were induced by three different strains of LAB: Lactobacillus acidophilus, Lactobacillus delbrueckii spp. bulgaricus, Bifidobacterium bifidum. Tested strains were mixed together, in combinations with each other (pairs) or alone. Both, the LAB mixture as well as the pairs and the single LAB strains induced low lymphocyte proliferation (about 10% of ConA-induced response). However, the single LAB strains and their combinations were quite different cytokines inducers. First, L. acidophilus was much stronger IFN-gamma inducer than the LAB mixture, being a few times higher IL-12 stimulator than L. bulgaricus and B. bifidum. Second, L. bulgaricus and B. bifidum suppressed L.acidophilus-induced IFN-gamma synthesis to the level equal to that induced by the LAB mixture, limiting IL-12 production by about 30% and 70%, respectively. Third, the LAB strains were good IL-10 and TNF-alpha inducers, irrespectively of their combinations used. We conclude that LAB strains' pro or anti-inflammatory potentials are at least in part dependent on their composition. Low LAB mixture-induced IL-12 and IFN-gamma production and relatively high IL-10 and TNF-alpha expression may represent cellular activities normally induced in vivo by a combined action of bacterial antigens. Their presence is important to limit pro-inflammatory reactions (via IL-10) and to provide protection against infections (via TNF-alpha).

Reduction of naive CD4/CD45RA+ T cells in children with biliary atresia before and after liver transplantation.

The aim of this study was to examine whether liver transplantation reverses the abnormal distribution of lymphocyte subsets previously observed in biliary atresia children, namely a selective decrease in the naive CD4/CD45RA+ T cell subset and an increase in the B and natural killer cell subpopulations. Eight biliary atresia children aged 1.08 to 6 years were studied before and 1 year after LTx for comparison with 15 age-matched healthy controls. The posttransplant immunosuppressive regimens included prednisone [0.1 mg/kg] and tacrolimus (level range: a 10-12 microg/dL). The percentage, absolute cell number, and receptor density were assessed by the use of double color flow cytometry (EPICS-XL MCL fluorocytometer). Biliary atresia patients were compared after LTx with subjects before LTx, essentially showing no statistically significant changes in lymphocyte subsets. We conclude that LTx of biliary atresia children does not reverse the abnormal lymphocyte subset distribution present before transplantation. Hence, these changes may reflect either their independence from the liver status or may result from immunosuppressive treatment that contributes to defective CD4+ T cell regeneration reflected by a deficiency in CD4/CD45RA+ naive T cells.

Abnormalities in the T and NK lymphocyte phenotype in patients with Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by spontaneous chromosomal instability with predisposition to immunodeficiency and cancer. In order to assess the cellular basis of the compromised immune response of NBS patients, the distribution of functionally distinct lymphocyte subsets in peripheral blood was evaluated by means of double-colour flow cytometry. The study involved the 36 lymphopenic patients with a total lymphocyte count < or =1500 microl (group A) and seven patients (group B) having the absolute lymphocyte count comparable with the age-matched controls (> or =3000 microl). Regardless of the total lymphocyte count the NBS patients showed: (1) profound deficiency of CD4+ and CD3/CD8+ T cell subsets and up to fourfold increase in natural killer (NK) cells, almost lack of naive CD4+ T cells expressing CD45RA isoform, unchanged percentage of naive CD8+ cell subset (CD8/CD45RA+) but bearing the CD8 receptor of low density (CD8low); (2) normal expression of CD45RA isoform in the CD56+ lymphocyte subset, profound decrease in alpha beta but up to threefold increase in gamma delta-T cell-receptor (TCR)-positive T cells; (3) shift towards the memory phenotype in both CD4+ and CD8+ lymphocyte subpopulations expressing CD45RO isoform (over-expression of CD45RO in terms of both the fluorescence intensity for CD45RO isoform and the number of positive cells); and (4) an increase in fluorescence intensity for the CD45RA isoform in NK cells population. These results indicate either a failure in T cell regeneration in the thymic pathway (deficiency of naive CD4+ cells) and/or more dominant contribution of non-thymic pathways in lymphocyte renewal reflected by an increase in the population of CD4+ and CD8+ memory cells, gamma delta-TCR positive T as well as NK cell subsets.

Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis.

BACKGROUND: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. METHODS: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing 'naive' (CD45RA+) and 'memory' (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. RESULTS: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD19+ cells and NK lymphocytes; 2) a reduction in the percentage of 'naive' CD4+ but normal proportion of 'naive' CD8+ as well as CD4+ and CD8+ 'memory' cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of 'naive' and 'memory' T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. CONCLUSIONS: It is concluded that the reduction in number of 'suppressor-inducer-like 'naive' CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.

IGF-I triple helix gene therapy of rat and human gliomas.

PURPOSE: IGF-I anti-gene technology was applied in treatment of rat and human gliomas using IGF-I triple helix approach. MATERIAL AND METHODS: CNS-1 rat glioma cell and primary human glioblastoma cell lines established from surgically removed glioblastomas multiforme were transfected in vitro with IGF-I antisense (pMT-Anti-IGF-I) or IGF-I triple helix (pMT-AG-TH) expression vectors. The transfected cells were examined for immunogenicity (immunocytochemistry and flow cytometry analysis) and apoptosis phenomena (electron microscopy). 3 x 10(6) transfected cells were inoculated subcutaneously either into transgenic Lewis rats or in patients with glioblastoma. The peripheral blood lymphocytes (PBL) derived from "vaccinated" patients were immunophenotyped for the set of CD antigens (CD4, CD8 etc). RESULTS: Using immunocytochemistry and Northern blot techniques, the transfected "antisense" and "triple-helix" cells showed total inhibition of IGF. Transfected cultures were positively stained either for both MHC-I and B7 antigens--60% of cloned lines, or for MHC-I only--40% of cloned lines. Moreover "triple helix" cells as compared to "antisense" cells showed slightly higher expression of MHC-I or B7. Transfected cells also showed the feature of apoptosis in 60%-70% of cells. In in vivo experiments with rats bearing tumors, the injection of "triple helix" cells expressing both MHC-I and B7 interrupted tumor growth in 80% of cases. In contrast, transfected cells expressing only MHC-I stopped development in 30% of tumors. In five patients with surgically resected glioblastoma who were inoculated with "triple helix" cells, PBL showed an increased percentage of CD4 + CD25+ and CD8 + CD11b-cells, following two vaccinations. CONCLUSIONS: The anti-tumor effectiveness of IGF-I anti-gene technology may be related to both MHC-I and B7 expression in cells used for therapy. The IGF-I antigene therapy of human glioblastoma multiforme increases immune response of treated patients.

Reduction of CD45RA Isoform Expression and Decrease in CD4 and CD8 Receptor Density in Lymphocytes of Patients with Primary Biliary Cirrhosis.

BACKGROUND: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. METHODS: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD 19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing 'naive' (CD45RA+) and 'memory' (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. RESULTS: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD 19+ cells and NK lymphocytes; 2) a reduction in the percentage of 'naive' CD4+ but normal proportion of 'naive' CD8+ as well as CD4+ and CD8+ 'memory' cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of 'naive' and 'memory' T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. CONCLUSIONS: It is concluded that the reduction in number of 'suppressor-inducer-like 'naive' CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.

Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: an 8-year follow-up study in a single centre.

During an 8-year period of observation, defects of immune responses were characterized and monitored in 40 of 50 Polish children with Nijmegen breakage syndrome referred to the Children's Memorial Health Institute in Warsaw. The following parameters were determined at diagnosis: (1) concentrations of serum IgM, IgG, IgA; (2) concentrations of IgG subclasses; and (3) lymphocyte subpopulations. In addition, naturally acquired specific antibodies against Streptococcus pneumoniae were determined in 20 patients with a history of recurrent respiratory infections. During follow-up, total serum immunoglobulins and IgG subclasses were monitored systematically in 17 patients who did not receive immunomodulatory therapy. Moreover, anti-HBs antibody response was measured after vaccination of 20 children against HBV. We found that the immune deficiency in NBS is profound, highly variable, with a tendency to progress over time. Systematic monitoring of the humoral response, despite good clinical condition, is essential for early medical intervention.

Deficiency of the expression of CD45RA isoform of CD45 common leukocyte antigen in CD4+ T lymphocytes in children with infantile cholestasis.

The immunological background of the pathological changes that appear in infantile cholestasis (infections, inflammatory process in the liver) is largely unknown. With the use of double color flow cytometry, we assessed the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 29 infants with extra and intra-hepatic cholestasis (12 and 17 patients, respectively), aged from 1 to 8.6 months. Control group consisted of 15 age-matched, healthy infants. We examined: (1) the expression of CD3, CD4, CD8, CD19 lymphocyte surface receptors; and (2) the distribution of lymphocyte subsets with distinctive surface Ag characteristics of 'naive' (CD45RA+) and 'memory' (CD45RO+) cells in both CD4+ and CD8+ cell populations. The surface markers expression was evaluated in terms of percentage of positive cells and receptor density. The following changes in the expression of lymphocyte surface markers are described: (1) a decrease in the percentage of total CD3+, CD4+ cells but normal percentage of CD8+ cells and elevated proportion of CD19+ B cells; (2) a reduction of the proportion of 'naive' CD4+ lymphocytes but normal percentage of 'naive' CD8+ as well as 'memory' CD4+ and CD8+ cell subsets; (3) a decrease in density of CD3, CD4+, CD8 receptors, and D45RA isoform in a subset of 'naive' CD4+ cells. We conclude that deficiency of 'naive' CD4+ T cell subset which possess important effector and immunoregulatory functions, and low expression of certain lymphocyte receptors known to be engaged in T cell activation, possibly reflect a defect of cell mediated immunity that may account for viral and bacterial infections, often observed in infants with cholestasis.

Immunological abnormalities in children with biliary atresia.

Since orthotopic liver transplantation is the treatment of choice for bilary atresia, the role of nutritional support preceding this procedure is significant. The aim of this study was to assess the selected parameters of both humoral and cellular immunity before and after nutritional support. Eight children aged 1.08-7 years. with biliary atresia, qualified to LTx, received high-calorie standard diet supplemented with MCT oil. The distribution of functionally different lymphocyte subpopulations in the peripheral blood was evaluated using double color flow cytometry (EPICS-MCL, Coulter). The concentrations of total serum immunoglobulins were measured by nephelometry (Beckman Array 360) and concentrations of IgG subclasses by ELISA. Abnormalities in the expression of lymphocyte surface markers as well as in immunoglobulin synthesis were as follows: 1) decrease in the percentage of total CD3+ (4/8), CD4+ (5/8), CD8+ (3/8) cells and markedly elevated percentage of CD19+ B cells (4/8); 2) reduction of the proportion of 'naive' CD4+ and CD8+ lymphocytes but normal percentage of 'memory' CD4+ and CD8+ cell subsets; 3) hypergammaglobulinemia with especially high levels of IgG (16.0-3.05 g/l) and IgA (2.6-6.66 g/l) was found in 6 out of 8 children. Treatment with hypercaloric diet did not improve the immunological parameters. We conclude that lymphopenia and possibly also hypergammaglobulinemia observed in BA children resulted mainly from the deficiency of the so-called 'naive', suppressor-inducer CD4+ T cell subset (CD4+/CD45RA+) that is known to maintain the proper level of immunoglobulin synthesis by inhibition of B cell differentiation into plasma cells.

Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome.

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ ("naive" helper T cells, suppressor-inducer), CD45RA+CD8+ ("naive" suppressor T cells, suppressor-effector), CD45RO+CD4+ ("memory" helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-gamma, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18+/-0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05+/-0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2+/-0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82+/-0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85+/-0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5+/-0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS.

Effect of Pseudomonas aeruginosa exotoxin A on IFN-gamma synthesis: expression of costimulatory molecules on monocytes and activity of NK cells.

The aim of the study was (1) to evaluate the effect of Pseudomonas aeruginosa Exotoxin A (P-ExA) on the production of IFN-gamma in anti-CD3 induced human peripheral blood mononuclear cells (PBMC) and (2) to establish the effect of P-ExA on the IFN-gamma dependent cellular activities such as the expression of costimulatory molecules on monocytes and cytotoxicity of NK cells. The toxin in a high dose (100 ng/ml) inhibited IFN-gamma synthesis. Inhibitory effect of P-ExA was abolished by IL-1alpha which in a combination with P-ExA exerted a strong synergistic effect on IFN-gamma synthesis. Other monokines such as IL-1beta, IL-6, TNF-alpha neither reversed the inhibitory effect of P-ExA nor induced production of IFN-gamma. P-ExA also inhibited IFN-gamma-induced cellular events: (1) expression of costimulatory molecules on monocytes (CD80, CD86, ICAM-1, HLA-DR); (2) cytotoxic activity of NK cells. Inhibition of NK cells activity by P-ExA was not reversed by cytokines such as IL-2, IFN-alpha and TNF-alpha, which are known to enhance effector functions of NK cells. From these results we conclude that: (1) inhibition of IFN-gamma synthesis, as well as IFN-gamma-induced expression of costimulatory molecules and NK-cell effector functions may lead to suppression of specific and non-specific defense mechanisms, respectively, which are necessary for elimination of PA bacteria; (2) enhancement of IFN-gamma synthesis induced by P-ExA in a combination with IL-1alpha may cause harmful, Th1 cells dependent, inflammatory reactions of the host (septic shock, tissue damage) during infection with Pseudomonas aeruginosa.

Further delineation of the classical Smith-Lemli-Opitz syndrome phenotype at different patient ages: clinical and biochemical studies.

We present here extensive clinical and biochemical data on thirteen SLOS (type I) patients with proven defect in cholesterol biosynthesis for further delineation of the classical SLOS phenotype at different patient ages.

Effect of Pseudomonas aeruginosa exotoxin A on CD3-induced human T-cell activation.

The effect of Pseudomonas aeruginosa (PA) exotoxin A (P-ExA) on CD3-induced T-cell activation was studied on the level of T-cells (proliferation, synthesis of interleukin (IL)-2, expression of IL-2R complex, ICAM-1,2 and LFA-1 molecules), and on the level of monocytes (expression of ICAM-1,2, LFA-1 molecules, as well as FcRI and CD14 receptors). We found that: (1) P-ExA blocked T-cell proliferation and this effect was totally reversed by intact monocytes, and partially by IL-2 or TPA but not by costimulatory cytokines (IL-1alpha, IL-1beta, TNF-alpha or IL-6); (2) P-ExA transiently, in short-term cultures (48 h), inhibited synthesis of IL-2; (3) prolonged stimulation (96 h) of peripheral blood mononuclear cells (PBMC) or CD4 + T-cells with P-ExA in high or low doses (100 and 10 ng/ml, respectively), enhanced the level of IL-2 in the cultures; (4) P-ExA at low dose, combined with IL-1beta, TNF-alpha or IL-6, up-regulated synthesis of IL-2; and (5) stimulation of T-cells with anti-CD3 monoclonal antibody (mAb) and P-ExA at high dose diminished the expression of the p55 chain but not of the p75 chain of IL-2R complex and slightly affected the expression of CD3 complex, ICAM-1,2 and LFA-1 molecules. Hence, P-ExA can regulate the level of IL-2 in cultures of CD3-induced T-cells either by inhibition of IL-2 consumption (when P-ExA is applied in high dose), or by induction of IL-2 production (a costimulatory effect exerted by P-ExA in low dose in combination with monokines). Action of P-ExA on monocytes resulted in: (1) inhibition of the expression of ICAM-1,2 molecules and their ligand LFA-1 molecule; (2) low expression of FcRI receptor (a ligand for Fc part of CD3 mAb); and (3) inhibition (over 90%) of the expression of CD14 molecule. In conclusion, P-ExA-induced anergy of T-cells depends on: (a) decrease in the affinity of IL-2R complex on activated T-cells; and (b) inhibition of the accessory activities of monocytes.

Kabuki (Niikawa-Kuroki) syndrome associated with immunodeficiency.

We report a case of a 19-year-old male with the cardinal features of the Kabuki syndrome (KS) and, in addition, with severe immunodeficiency. Finding immune deficiency in a KS patient, prompted us to determine whether this association was related to a deletion within the DiGeorge chromosomal region. Fluorescence in situ hybridization (FISH) with the Oncor probe N25(D22S75) revealed no deletion of 22q11.2 in the patient.

Linkage studies exclude the AT-V gene(s) from the translocation breakpoints in an AT-V patient.

An 8-year-old girl with severe microcephaly of prenatal onset, borderline intelligence, defects of skin pigmentation, deficiency of both humoral and cellular immunity, a normal serum alpha-fetoprotein level and hypersensitivity to ionizing irradiation is described. Spontaneous chromosomal breakage in lymphocytes together with the clinical presentation led to the diagnosis of ataxia telangiectasia variant (AT-V). In addition, the patient carried a constitutional translocation of paternal origin: 46,XX,t(3;7)(q12;q31.3) pat. In subsequent linkage and haplotype studies in 12 AT-V families with microsatellite markers from each of the translocation breakpoint regions, we could clearly exclude the localization of an AT-V gene to these regions.

[Regulation of Ige synthesis and cytokines in selected allergic diseases]. / Regulacja syntezy IgE oraz cytokin w wybranych zespolach alergicznych.

Some of CD4+ helper T cells-mediated mechanisms of IgE synthesis were discussed. The present division of helper T cells population into Th1 and Th2 subsets reflects their role in the induction as well as in the control of immune response. The Th1 cells are involved mainly in the cellular immune responses, and Th2 cells in the humoral immune responses, including IgE synthesis. Development of investigations on cytokines and evaluation of their influence on regulation of IgE synthesis may have a role in the treatment of allergic diseases in the future.

Eleven Polish patients with microcephaly, immunodeficiency, and chromosomal instability: the Nijmegen breakage syndrome.

We report on 11 patients from 8 independent families (3 pairs of sibs) with a complex clinical pattern including microcephaly, peculiar "bird-like" face, growth retardation, and, in some cases, mild-to-moderate mental deficiency. Most of the patients have recurring respiratory tract infections. One girl has developed B-cell lymphoma. A detailed anthropometric study of 15 physical parameters, including 3 cephalic traits, was performed. It was possible to study the chromosomes of PHA-stimulated lymphocytes in all of the patients. We found structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14 in a proportion of metaphases in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were hitherto studied in this respect. Our patients fulfill the criteria of the Nijmegen breakage syndrome, which belongs to the growing category of ataxia telangiectasia-related genetic disorders. In light of the increased predisposition to malignancy in this syndrome, an accurate diagnosis is important for the patient.

Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM-1 and HLA-DR/Ia molecules.

This study was undertaken to evaluate the monocyte function of uraemic non-responders to hepatitis B vaccination. Therefore, some parameters concerning antigen processing by monocytes (Mo) as antigen presenting cells (APC) were analysed. It was found that in uraemic non-responders, (1) the internalization of HBsAg by monocytes was significantly decreasjed-HBsAg complexed with specific IgG or as immune complex isolated from patients is better internalized compared with free HBsAg; (2) during antigen presentation the expression of adhesion (ICAM-1) and accessory (HLA-DR/Ia) molecules was significantly decreased in uraemic patients, especially in non-responders; and (3) impaired internalization of HBsAg as well as a decrease in ICAM-1 and HLA-DR/Ia expression, correlated well with the blunted proliferation of CD4(+) T cells stimulated by autologous monocytes induced by HBsAg.